|
If you are seeing this message, you may be experiencing temporary network problems. Please wait a few minutes and refresh the page. If the problem persists, you may wish to report it to your local Network Manager.
It is also possible that your web browser is not configured or not able to display style sheets. In this case, although the visual presentation will be degraded, the site should continue to be functional. We recommend using the latest version of Microsoft or Mozilla web browser to help minimise these problems.
Wiley InterScience | ||||||||||||
  Neuropathology and Applied NeurobiologyVolume 33 Issue 4, Pages 440 - 454 Published Online: 5 Jul 2007 © 2010 Blackwell Publishing Journal of the British Neuropathological Society
Abstract | References | Full Text: HTML, PDF (Size: 643K) | Related Articles | Citation Tracking  Genetic intratumour heterogeneity in high-grade brain tumours is associated with telomere-dependent mitotic instability Copyright 2007 Blackwell Publishing Ltd KEYWORDS anaphase bridge • clonal evolution • genomic instability • glioblastoma multiforme • telomere • xenograft C. Glanz, J. Rebetz, Y. Stewénius, A. Persson, E. Englund, N. Mandahl, F. Mertens, L. G. Salford, B. Widegren, X. Fan and D. Gisselsson (2007) Neuropathology and Applied Neurobiology33, 440–454 Genetic intratumour heterogeneity in high-grade brain tumours is associated with telomere-dependent mitotic instability ABSTRACTGlioblastoma multiforme (GBM) and other high-grade brain tumours are typically characterized by complex chromosome abnormalities and extensive intratumour cytogenetic heterogeneity. The mechanisms behind this diversity have been little explored. In this study, we analysed the pattern of chromosome segregation at mitosis in 20 brain tumours. We found an abnormal segregation of chromatids at mitosis through anaphase bridging (10–25% of anaphase cells) in all 10 GBMs. Anaphase bridging was also found in two medulloblastomas (7–15%), one anaplastic astrocytoma (17%) and one oligodendroglioma (6%). These tumours showed a relatively high degree of cytogenetic complexity and heterogeneity. In contrast, cell division abnormalities were not found in low-grade brain tumours with less complex karyotypes, including two pilocytic astrocytomas and two ependymomas. Further analysis of two GBMs by fluorescence in situ hybridization with telomeric repeat probes revealed excessive shortening of TTAGGG repeats, indicating dysfunctional protection of chromosome ends. In xenografts established from these GBMs, there was a gradual reduction in cytogenetic heterogeneity through successive passages as the proportion of abnormally short telomeres was reduced and the frequency of anaphase bridges decreased from >25% to 0. However, bridging could be reintroduced in late-passage xenograft cells by pharmacological induction of telomere shortening, using a small-molecule telomerase inhibitor. Telomere-dependent abnormal segregation of chromosomes at mitosis is thus a common phenomenon in high-grade brain tumours and may be one important factor behind cytogenetic intratumour diversity in GBM. Received 12 September 2006 | 
|
